The goal of this series of challenge studies is to examine the impact of menstrual cycle phase on cortical GABA response to administration of agents with either direct (benzodiazepines) or indirect (progesterone, fluoxetine) GABA modulating properties. While the impact of these agents on cortical GABA levels in women with premenstrual dysphoric disorder (PMDD) is of interest, this study is designed primarily for those women without a psychiatric illness.

To determine the impact of GABA-A receptor agonists (benzodiazepines, allopregnanolone) and other GABA-modulating agents (fluoxetine) on cortical GABA levels by menstrual cycle phase as measured using 1H-MRS in healthy controls. [ Time Frame: Each medication will be administered 2 times during a 1-month menstrual cycle. ] [ Designated as safety issue: No ]

Zolpidem will be administered twice to each participant; once in the follicular and luteal phases of the menstrual cycle.

Drug: Zolpidem

Zolpidem 10 mg by mouth in the follicular and luteal phase of the menstrual cycle per participant.

Other Name: Ambien

Experimental: Progesterone 2

Progesterone will be administered twice to each participant; once in both the follicular and luteal phases of the menstrual cycle.

Drug: Progesterone

Progesterone 800 mg by mouth will be administered to each participant once in the follicular and luteal phases of the menstrual cycle.

Other Name: Prometrium

Experimental: Fluoxetine 3

Fluoxetine will be administered twice to each participant; once in both the follicular and luteal phases of the menstrual cycle.

Drug: Fluoxetine

Fluoxetine 20 mg by mouth in the follicular and luteal phase of the menstrual cycle per participant.

Other Name: Prozac

Eligibility

Ages Eligible for Study:

18 Years to 45 Years (Adult)

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Women ages 18-45 and able to give voluntary written informed consent;

Regular menstrual periods of 24-35 days in length;

Body mass index 18.5 to 30 kg/m2;

No past or present DSM-IV psychiatric or substance dependence diagnosis by structured diagnostic interview (SCID-NP); no substance abuse history within the previous 2 years;

Absence of mood symptoms across the menstrual cycle during one month of prospective daily ratings with the Daily Record of Severity of Problems (DRSP); the DRSP is based on the DSM-IV research criteria for premenstrual dysphoric disorder (PMDD) and has been used in numerous studies to confirm the presence or absence of significant premenstrual mood and behavioral difficulties;

Must be willing and able to participate in at least three of the four challenge paradigms.

Family history of first degree relative with an Axis I psychiatric or substance dependence disorder (excepting alcohol and nicotine) (per subject report);

Current treatment with psychoactive medication;

Diabetes controlled by means other than diet;

Use of steroid contraceptives (any method involving hormones) within the previous 4 months;

Habitual consumption of more than 7 alcoholic drinks per week or more than 2 drinks on any particular occasion; must be willing to abstain from alcohol consumption for 48 hours prior to each 1H-MRS scan;

Implanted metallic devices.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00676026

Locations

United States, Connecticut

Yale University School of Medicine; Yale Program for Women's Reproductive Behavioral Health